Phospholipase A2 Antagonists Inhibit Constitutive Retrograde Membrane Traffic to the Endoplasmic Reticulum

Abstract

Eukaryotic cells contain a variety of cytoplasmic Ca²⁺‐dependent and Ca²⁺‐independent phospholipase A₂s (PLA₂s; EC 2.3.1.2.3). However, the physiological roles for many of these ubiquitously‐expressed enzymes is unclear or not known. Recently, pharmacological studies have suggested a role for Ca²⁺‐independent PLA₂ (iPLA₂) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)‐stimulated membrane tubulation and Golgi‐to‐endoplasmic reticulum (ER) retrograde membrane trafficking, in particular. Here, we extend these studies to show that membrane‐permeant iPLA₂ antagonists potently inhibit the normal, constitutive retrograde membrane trafficking from the trans‐Golgi network (TGN), Golgi complex, and the ERGIC‐53‐positive ER‐Golgi‐intermediate compartment (ERGIC), which occurs in the absence of BFA. Taken together, these results suggest that iPLA₂ enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events.